We established a steroidogenic human ovarian granulosa-like tumor cell line, designated KGN, from a patient with invasive ovarian granulosa cell carcinoma. KGN had a relatively long population doubling time of about 46.4 h and had an abnormal karyotype of 45,XX, 7q-, -22. A steroid analysis of the cultured medium by RIA performed 5 yr after the initiation of culture showed that KGN was able to secrete pregnenolone and progesterone, and both dramatically increased after stimulation with (Bu)(2)cAMP. However, little or no secretion of 17alpha-hydroxylated steroids, dehydroepiandrosterone, androstenedione, or estradiol was observed. The aromatase activity of KGN was relatively high and was further stimulated by (Bu)(2)cAMP or FSH. These findings showed a pattern similar to that of steroidogenesis in human granulosa cells, thus allowing analysis of naturally occurring steroidogenesis in human granulosa cells. Fas-mediated apoptosis of KGN was also observed, which mimicked the physiological regulation of apoptosis in normal human granulosa cells. Based on these findings, this cell line is considered to be a very useful model for understanding the regulation of steroidogenesis, cell growth, and apoptosis in human granulosa cells.
The effectiveness of the prophylactic chemotherapy was evaluated in 420 patients with molar pregnancy. All patients were followed for 5 to 15 years after the evacuation. Twenty-two (7.5%) of 293 patients with prophylactic chemotherapy and 23 (18.1%) of 127 patients without prophylactic chemotherapy (control) developed secondary trophoblastic disease. The prophylactic chemotherapy could reduce the occurrence of secondary trophoblastic disease. In these secondary trophoblastic diseases, 5 (22.7%) of 22 patients in the prophylactic chemotherapy group and 5 (21.7%) of 23 in the control had metastatic trophoblastic disease. Choriocarcinoma after the molar pregnancy developed in two patients (0.7%) of the prophylactic chemotherapy group and two (1.6%) of the control. Prophylactic chemotherapy did not eliminate the occurrence of choriocarcinoma. The complication of the prophylactic chemotherapy was seen in 27.3% of the patients. Neither severe complication nor death were related to the toxicity.
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